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The aim of this study was to evaluate the factors, which affect insulin release and stability in simulated gastrointestinal fluid that ultimately will reduce the bioavailability of insulin in a nanoparticulate oral delivery system. The focus was on nanoparticulate carriers developed by C. Reis, which have the highest level of bioavailability reported in the literature thus far. Particles observed by TEM were spherical and particle analyzer data showed that the peak of the distribution was 10 nm. Entrapment efficiency of insulin was 85%. Insulin retention/release was evaluated in both enzymatic and enzyme-free simulated digestive fluids. HPLC measurement showed that insulin was stable in acid condition in presence and absence of pepsin. By changing the pH to 6.8 in an intestinal simulation, the amount of insulin decreased such that at the end of the 5 h simulation, 71% of the insulin was measureable in simulated GI fluid in presence of enzymes. Insulin release profile from nanoparticles was low in gastric condition. After changing the pH to 6.8, an initial release of insulin occurred in the first 1h followed by plateau state in the remaining 2h. After a total of 5h in acidic followed by neutral pH medium, the formulation retained 48% of the insulin in the particles in simulated GI fluid in presence of enzyme. As confirmation of the amount of retained insulin, after 5h, particles were dissolved and the formulation was shown to fully retain up to 45% of the insulin in extended simulated gastrointestinal condition in the presence of enzymes. Insulin release behavior was investigated in different simulated small intestinal media by incorporating phosphate buffer or bicarbonate buffer and physiological electrolytes. The release rate from particles in the phosphate buffer was faster compared to bicarbonate buffers. KBB-C showed a release profile that was very different from other media, with about 10% released in the first 30 min and 70% of the insulin remaining entrapped within the particles at the end of the experiment. Release in this buffer was reduced due to the decreased sodium to calcium ratio compared to the other KBB media. / Thesis (Master, Chemical Engineering) -- Queen's University, 2013-08-26 13:02:50.837

Ph.D., Faculty of Health Sciences. University of the Witwatersrand, 2011

Often associated with chemotherapy are the dangerous and sometimes lifethreatening side effects towards non-cancerous tissue that can occur while on such drug regimens. The design and utilization of macromolecular drug delivery vehicles is gaining much attention because the vascular system of tumor tissue possesses properties that make it permeable to macromolecules. The attachment or encapsulation of anticancer drugs to macromolecules can be used to selectively deliver these drugs to tumor tissue thereby minimizing the toxic effects towards healthy tissue while specifically targeting the tumor. Moreover, the association of poorly water soluble drugs with soluble macromolecules can increase the water solubility of such hydrophobic drugs. Finally, association of chemotherapeutic agents with macromolecules can also increase the drugs?? circulation time by decreasing the rate of renal clearance thus leading to improve pharmacokinetics. A class of spherical, hyperbranched polymers known as dendrimers has received much attention as potential vehicles for anticancer drug delivery. Dendrimers based on melamine might afford such use as macromolecular carriers for drug delivery. Therefore an evaluation of melamine dendrimers is reported. The goal of objective one was to assess both the in vitro and in vivo biocompatibilities of a cationic dendrimer based on melamine. The results reported herein indicate that this particular species of dendrimer is not suitable for in vivo use and did not warrant further investigation. The goals of objective two were to see what impact surface modification had on the in vitro and in vivo toxicities of a melamine dendrimer. The results presented here indicate that surface modification of a cationic dendrimer to anionic or neutral species can extensively increase biocompatibility. Moreover, the introduction of neutral poly(ethylene glycol) (PEG) grafts affords the most protection in vitro and in vivo. Interaction with albumin, controlled drug release, cellular uptake along with favorable biodistribution patterns are vital factors that must be evaluated when screening a drug delivery system. Evaluating the PEGylated dendrimer as a vehicle for anticancer drug delivery, the goal of objective three, provides initial evidence that the PEGylated dendrimer displays favorable characteristics as a vehicle for drug delivery and justifies additional studies utilizing in vivo models.

Thesis (MPA) --University of Limpopo, 2011. / In this research report, I present the role of ethical principles in promoting efficient service delivery at the Department of Education in the Capricorn District of Limpopo Province. I critically present what the codes of conduct are; and explore the challenges and constraints faced by the public regarding behaviour and conduct of public officials Both the interviews and the questionnaires of the study were conducted at Capricorn District of the Department of Education at Lebowakgomo. The subjects of the study were all the current personnel attached to the Human Resource Management of the district.The report is concluded with an assessment of the challenges and constraints faced by the districttowards acceptable conduct as opposed to unacceptable or unethical behaviour, as well asrecommendations for addressing them.

Thesis (M.S.)--University of Michigan, 1985.

Thesis (M.S.)--University of Michigan, 1994.

Thesis (Ph. D.)--Northeastern University, 2008. / Title from title page (viewed Aug. 4, 2009). Graduate School, Bouvé College of Health Sciences, School of Pharmacy. Includes bibliographical references.

Thesis (Ph. D.)--University of Washington, 1999. / Vita. Includes bibliographical references (leaves 60-71).

Thesis (M.S.)--University of Michigan, 1985.